Is TH p.Gln428fs (c.1282del) pathogenic?

TH p.Gln428fs (c.1282del) is classified Likely pathogenic in TH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-03-23). No gnomAD frequency available for this variant; Associated with TH-deficient dopa-responsive dystonia.

What condition is associated with TH p.Gln428fs (c.1282del)?

TH p.Gln428fs (c.1282del) is associated with TH-deficient dopa-responsive dystonia (ClinVar).

How common is TH p.Gln428fs (c.1282del) in the general population?

TH p.Gln428fs (c.1282del) is no gnomAD frequency available for this variant (gnomAD).

How is Autosomal recessive dopa-responsive dystonia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TH p.Gln428fs

c.1282del · rs1554922434 · VCV551088

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

TH-deficient dopa-responsive dystonia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TH
Protein: p.Gln428fs
Coding: c.1282del
MANE Select: NM_000360
dbSNP: rs1554922434
Type: Deletion
Location: chr11:2165284 (GRCh38)
Gene constraint: LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 7 PDB
Residue 428: a UniProt-annotated variant site (in arsegs; phenotype with prominent levodopa-responsive myoconus-dystonia (m-d)); an α-helix

Full TH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TH-deficient dopa-responsive dystonia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive dopa-responsive dystonia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TH p.Gln428Ter Pathogenic ★★ same residue
TH p.Gln346fs Pathogenic/Likely pathogenic ★★ same condition
TH p.Glu375fs Pathogenic/Likely pathogenic ★★ same condition
TH p.His335fs Likely pathogenic ★★ same condition
TH p.Ser195fs Pathogenic/Likely pathogenic ★★ same condition
TH p.Ser404fs Pathogenic/Likely pathogenic ★★ same condition
TH p.Thr238fs Pathogenic/Likely pathogenic ★★ same condition
TH p.Val18fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/th-p-gln428fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown